We summarize here the progress in identifying the neuronal network as well as the function of paradoxical sleep and the gaps of knowledge that should be filled in priority. The core system generating paradoxical sleep localized in the brainstem is now well identified, and the next step is to clarify the role of the forebrain in particular that of the hypothalamus including the melanin-concentrating hormone neurons and of the basolateral amygdala. We discuss these two options, and also the discovery that cortical activation during paradoxical sleep is restricted to a few limbic cortices activated by the lateral supramammillary nucleus and the claustrum. Such activation nicely supports the findings recently obtained showing that neuronal reactivation occurs during paradoxical sleep in these structures, and induces both memory consolidation of important memory and forgetting of less relevant ones. The question that still remains to be answered is whether paradoxical sleep is playing more crucial roles in processing emotional and procedural than other types of memories. One attractive hypothesis is that paradoxical sleep is responsible for erasing negative emotional memories, and that this function is not properly functioning in depressed patients. On the other hand, the presence of a muscle atonia during paradoxical sleep is in favour of a role in procedural memory as new types of motor behaviours can be tried without harm during the state. In a way, it also fits with the proposed role of paradoxical sleep in setting up the sensorimotor system during development.

Moderate-intensity exercise is generally recommended for improving sleep, whereas, high-intensity exercise (HIE) prior to bedtime is often discouraged. We conducted a systematic review and meta-analysis to determine if acute or regular (chronic) HIE performed before bedtime disrupts nighttime sleep of healthy adult, good sleepers compared with a no-exercise control. Six databases (PubMed, EMBASE, Scopus, Web of Science, CENTRAL, and PsycINFO) were searched from inception to 31st May, 2021. Studies were experimental trials published in English language, objectively (polysomnography, actigraphy) and/or subjectively assessed sleep after evening HIE in sedentary and physically fit, good sleepers (aged 18-50 y old). The revised Cochrane risk of bias tool for randomized trials was used to assess risk of bias in the included studies. The random-effects model was used for the meta-analyses. We included 15 acute evening HIE studies in the meta-analysis with a total of 194 participants. Acute evening HIE ending 0.5-4 h before bedtime decreased rapid eye movement sleep (-2.34%; p = 0.002) compared with a no-exercise control. No other significant sleep changes occurred. A regular evening HIE did not disrupt nighttime sleep. Overall, acute evening HIE performed 2-4 h before bedtime does not disrupt nighttime sleep of healthy, young and middle-aged adults. PROSPERO, protocol registration number: CRD42020218299.

As one of the fundamental sleep states, rapid eye movement (REM) sleep is believed to be associated with dreaming and is characterized by low-voltage, fast electroencephalographic activity and loss of muscle tone. However, the mechanisms of REM sleep generation have remained unclear despite decades of research. Several models of REM sleep have been established, including a reciprocal interaction model, limit-cycle model, flip-flop model, and a model involving γ-aminobutyric acid, glutamate, and aminergic/orexin/melanin-concentrating hormone neurons. In the present review, we discuss these models and summarize two typical disorders related to REM sleep, namely REM sleep behavior disorder and narcolepsy. REM sleep behavior disorder is a sleep muscle-tone-related disorder and can be treated with clonazepam and melatonin. Narcolepsy, with core symptoms of excessive daytime sleepiness and cataplexy, is strongly connected with orexin in early adulthood.

Sleep may contribute to the long-lasting consolidation and processing of emotional memories. Experimental fear conditioning and extinction paradigms model the development, maintenance, and treatment of anxiety disorders. The literature provides compelling evidence for the involvement of rapid eye movement (REM) sleep in the consolidation of such memories. This meta-analysis correlated polysomnographic sleep findings with psychophysiological reactivity to the danger (CS+) and safety stimuli (CS-), to clarify the specific role of sleep stages before and after fear conditioning, extinction learning and extinction recall. Overall, there was evidence that more pre-learning sleep stage two and less slow wave sleep was associated with higher psychophysiological reactivity to the safety stimulus during extinction learning. Preliminary evidence found here support the role of REM sleep during the post-extinction consolidation sleep phase in clinical populations with disrupted sleep, but not in healthy controls. Furthermore, the meta-regressions found that sex moderated the associations between sleep and psychophysiological reactivity throughout the paradigm providing evidence for diverging correlations in male and females. Specifically, increased post-extinction REM was associated with poorer extinction and safety recall in females while the opposite was found in males. These results have implications for future research in the role of sleep in emotional memory processing.

Melanin-concentrating hormone (MCH)-expressing neurons located in the lateral hypothalamus are considered as an integral component of sleep-wake circuitry. However, the precise role of MCH neurons in sleep-wake regulation has remained unclear, despite several years of research employing a wide range of techniques. We review recent data on this aspect, which are mostly inconsistent, and propose a novel role for MCH neurons in sleep regulation.
While almost all studies using \"gain-of-function\" approaches show an increase in rapid eye movement sleep (or paradoxical sleep; PS), loss-of-function approaches have not shown reductions in PS. Similarly, the reported changes in wakefulness or non-rapid eye movement sleep (slow-wave sleep; SWS) with manipulation of the MCH system using conditional genetic methods are inconsistent. Currently available data do not support a role for MCH neurons in spontaneous sleep-wake but imply a crucial role for them in orchestrating sleep-wake responses to changes in external and internal environments.

Epilepsy is a common and debilitating neurological disease. When medication cannot control seizures in up to 40% of cases, surgical resection of epileptogenic tissue is a clinically and cost- effective therapy to achieve seizure freedom. To simultaneously resect minimal yet sufficient cortex, exquisite localization of the epileptogenic zone (EZ) is crucial. However, localization is not straightforward, given relative difficulty of capturing seizures, constraints of the inverse problem in source localization, and possible disparate locations of symptomatogenic vs. epileptogenic regions. Thus, attention has been paid to which state of vigilance best localizes the EZ, in the hopes that one or another sleep-wake state may hold the key to improved accuracy of localization. Studies investigating this topic have employed diverse methodologies and produced diverse results. Nonetheless, rapid eye movement sleep (REM) has emerged as a promising sleep-wake state, as epileptic phenomena captured in REM may spatially correspond more closely to the EZ. Cortical neuronal asynchrony in REM may spatially constrain epileptic phenomena to reduce propagation away from the source generator, rendering them of high localizing value. However, some recent work demonstrates best localization in sleep-wake states other than REM, and there are reports of REM providing clearly false localization. Moreover, synchronistic properties and basic mechanisms of human REM remain to be fully characterized. Amidst these uncertainties, there is an urgent need for recording and analytical techniques to improve accuracy of localization. Here we present a systematic review and quantitative analysis of pertinent literature on whether and how REM may help localize epileptogenic foci. To help streamline and accelerate future work on the intriguing anti-epileptic properties of REM, we also introduce a simple, conceptually clear set-theoretic framework to conveniently and rigorously describe the spatial properties of epileptic phenomena in the brain.

Orexin receptor antagonists are a relatively new hypnotic principle. Their influence on human sleep architecture is a point of debate that has not been systematically evaluated. Thus, we performed a systematic review to assess how these compounds effect sleep architecture in healthy and clinical human samples. Relevant articles were identified via searches of PubMed, Embase, the Cochrane central register of controlled trials, and clinicaltrials. gov. From 1147 retrieved records, 18 satisfied inclusion criteria and formed the basis of this review. Of these, fifteen studies administered dual orexin receptor antagonists (DORA) in a healthy control (five studies) or clinical sample (ten studies). By contrast, three studies administered selective orexin receptor-2 antagonists (2-SORA) in either a healthy control (one study) or clinical sample (two studies). Results reveal DORAs increase total sleep time primarily by promoting REM sleep, without affecting, or even decreasing, non-REM sleep, especially in clinical samples. Therefore, the clinical utility of DORAs may depend on the specific sample being treated. For 2-SORAs, limited evidence available precludes firm conclusions about their influence on human sleep architecture and, thus, further investigation of 2-SORAs is required to define their effects and make comparisons on this basis with DORAs.

Polysomnographic studies have been performed to examine sleep abnormalities in posttraumatic stress disorder (PTSD), but clear associations between PTSD and sleep disturbances have not been established. A systematic review of the evidence examining the polysomnographic changes in PTSD patients compared with controls was conducted using MEDLINE, EMBASE, All EBM databases, PsycINFO, and CINAHL databases. Meta-analysis was undertaken where possible. The searches identified 34 studies, 31 of which were appropriate for meta-analysis. Pooled results indicated decreased total sleep time, slow wave sleep and sleep efficiency, and increased wake time after sleep onset in PTSD patients compared with healthy controls. PTSD severity was associated with decreased sleep efficiency and slow wave sleep percentage. Rapid eye movement (REM) sleep percentage was significantly decreased in PTSD patients compared with controls in studies including participants with mean age below 30 y, but not in studies with other mean age groups (30-40 y and >40 y). Our study shows that polysomnographic abnormalities are present in PTSD. Sex, age, PTSD severity, type of controls, medication status, adaptation night, polysomnographic scoring rules and study location are several of the demographic, clinical and methodological factors that contribute to heterogeneity between studies.

UNASSIGNED: The incubus phenomenon is a paroxysmal sleep-related disorder characterized by compound hallucinations experienced during brief phases of (apparent) wakefulness. The condition has an almost stereotypical presentation, characterized by a hallucinated being that exerts pressure on the thorax, meanwhile carrying out aggressive and/or sexual acts. It tends to be accompanied by sleep paralysis, anxiety, vegetative symptoms, and feelings of suffocation. Its prevalence rate is unknown since, in prior analyses, cases of recurrent isolated sleep paralysis with/without an incubus phenomenon have been pooled together. This is unfortunate, since the incubus phenomenon has a much greater clinical relevance than isolated sleep paralysis.
UNASSIGNED: PubMed, Embase, and PsycINFO were searched for prevalence studies of the incubus phenomenon, and a meta-analysis was performed.
UNASSIGNED: Of the 1,437 unique records, 13 met the inclusion criteria, reporting on 14 (k) independent prevalence estimates (total N = 6,079). The pooled lifetime prevalence rate of the incubus phenomenon was 0.19 [95% confidence interval (CI) = 0.14-0.25, k = 14, N = 6,079] with heterogeneous estimates over different samples. In selected samples (e.g., patients with a psychiatric disorder, refugees, and students), prevalence rates were nearly four times higher (0.41, 95% CI = 0.25-0.56, k = 4, n = 1,275) than in the random samples (0.11, 95% CI = 0.08-0.14, k = 10, n = 4,804). This difference was significant (P < 0.001).
UNASSIGNED: This review and meta-analysis yielded a lifetime prevalence of the incubus phenomenon in the general population of 0.11 and, in selected samples, of 0.41. This is slightly higher than the prevalence rates in previous analyses that included cases of recurrent isolated sleep paralysis without an incubus phenomenon. Based on the condition\'s robust clinical presentation and the relatively high prevalence rates, we advocate inclusion of the incubus phenomenon as a diagnostic category in major classifications such as the International Classification of Diseases and Related Health Problems and the Diagnostic and Statistical Manual of Mental Disorders. Recommendations are also made for clinical practice and future research.